Polymersomes-mediated delivery of CSF1R inhibitor to tumor associated macrophages promotes M2 to M1-like macrophage repolarization

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Rodriguez-Perdigon, Manuel and Jimaja, Sètuhn and Haen, Laetitia and Bruns, Nico and Rothen-Rutishauser, Barbara and Rüegg, Curzio (2022) Polymersomes-mediated delivery of CSF1R inhibitor to tumor associated macrophages promotes M2 to M1-like macrophage repolarization. Macromolecular Bioscience, 22 (8). 2200168. ISSN 1616-5187 (https://doi.org/10.1002/mabi.202200168)

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Abstract

The crosstalk between cancer cells and tumor associated macrophages (TAMs) within the tumor environment modulates tumor progression at all stages of cancer disease. TAMs are predominantly M2-like polarized macrophages with tumor-promoting activities. Nonetheless, they can be repolarized to tumoricidal M1-like macrophages through macrophage colony stimulating factor 1 receptor inhibition (CSF1Ri). CSF1Ri is being explored as multifaced therapeutic approach to suppress TAMs tumor-promoting functions and reduce cancer cell aggressiveness and viability. However, treatment with CSF1Ri results in significant TAMs death, thereby extinguishing the possibility of generating tumoricidal M1-like macrophages. Immunotherapy has not only improved overall patient's survival in some cancer types, but also caused frequent off-target toxicity. Approaches to balance efficacy versus toxicity are needed. Herein, a CSF1Ri-loaded polymersomes (PMs) based delivery platform is developed to promote M2-like macrophage repolarization. When testing in vitro on primary human monocyte-derived macrophages (MDMs), CSF1Ri-loaded PMs are preferentially taken up by M2-like macrophages and enhance M2 to M1-like macrophage repolarization while minimizing cytotoxicity in comparison to the free drug. When testing in a MDMs-MDA-MB-231 breast cancer cell coculture model, CSF1Ri-loaded PMs further retain their M2 to M1-like macrophages polarization capacity. This CSF1Ri-loaded PM-based platform system represents a promising tool for macrophage-based immunotherapy approaches.

ORCID iDs

Rodriguez-Perdigon, Manuel, Jimaja, Sètuhn, Haen, Laetitia, Bruns, Nico ORCID logoORCID: https://orcid.org/0000-0001-6199-9995, Rothen-Rutishauser, Barbara and Rüegg, Curzio;
CORE (COnnecting REpositories)